An update on the molecular actions of fenofibrate and its clinical effects on diabetic retinopathy and other microvascular end points in patients with diabetes.
An update on the molecular actions of fenofibrate and its clinical effects on diabetic retinopathy and other microvascular end points in patients with diabetes.
复制标题
DOI：
10.2337/db13-0800
复制
发表时间：
2013-12
期刊：
影响因子：
7.7
通讯作者：
Lamoureux EL
中科院分区：
文献类型：
--
作者：
Noonan JE;Jenkins AJ;Ma JX;Keech AC;Wang JJ;Lamoureux EL
非诺贝特药物作为治疗糖尿病视网膜病变（DR）和其他糖尿病引起的微血管并发症的新型药物而受到广泛关注。这种兴趣源于最近两项精心设计的大型临床试验，这些试验表明，2 型糖尿病患者除了肾脏和神经系统结果减少外，DR 的进展也大大减少，激光干预的需求也大大减少。在这两项试验中，在基线时患有 DR 的患者中观察到对 DR 进展的最大益处。最初被认为是一种调脂药物，现在看来，多种机制可能支持非诺贝特对糖尿病微血管终点的益处。非诺贝特调节许多不同基因的表达，对脂质控制、炎症、血管生成和细胞凋亡具有一系列有益作用。无论潜在的糖尿病病因如何，这些因素被认为在 DR 的发展中很重要。细胞实验表明，糖尿病条件下视网膜内皮细胞和色素上皮细胞的存活率得到提高，同时应激信号传导减少。此外，非诺贝特可改善糖尿病和视网膜新生血管形成的啮齿动物模型的视网膜结果。鉴于这些临床前研究的结果，需要进一步的临床试验来确定非诺贝特对其他形式的糖尿病（包括 1 型糖尿病）的益处。在 DR 管理中，非诺贝特可能是可改变的危险因素控制和定期眼科检查的有用辅助治疗。随着更多信息的出现，应不断修订将其纳入临床实践。
The drug fenofibrate has received major attention as a novel medical treatment for diabetic retinopathy (DR) and other diabetes-induced microvascular complications. This interest stems from two recent large, well-designed clinical trials that demonstrated large reductions in the progression of DR and the need for laser intervention, in addition to a reduction in renal and neurological outcomes, in patients with type 2 diabetes. In both trials, the greatest benefit on DR progression was observed in those patients with DR at baseline. Originally considered a lipid-modifying drug, it now appears that multiple mechanisms may underpin the benefit of fenofibrate on diabetic microvascular end points. Fenofibrate regulates the expression of many different genes, with a range of beneficial effects on lipid control, inflammation, angiogenesis, and cell apoptosis. These factors are believed to be important in the development of DR regardless of the underlying diabetes etiology. Cell experiments have demonstrated improved survival of retinal endothelial and pigment epithelial cells in conjunction with reduced stress signaling under diabetic conditions. Further, fenofibrate improves retinal outcomes in rodent models of diabetes and retinal neovascularization. Given the results of these preclinical studies, further clinical trials are needed to establish the benefits of fenofibrate in other forms of diabetes, including type 1 diabetes. In DR management, fenofibrate could be a useful adjunctive treatment to modifiable risk factor control and regular ophthalmic review. Its incorporation into clinical practice should be continually revised as more information becomes available.
登录
查看更多内容
DOI：
10.1056/nejmoa1001288
发表时间：
2010-07-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
ACCORD Study Group;ACCORD Eye Study Group;Chew EY;Ambrosius WT;Davis MD;Danis RP;Gangaputra S;Greven CM;Hubbard L;Esser BA;Lovato JF;Perdue LH;Goff DC Jr;Cushman WC;Ginsberg HN;Elam MB;Genuth S;Gerstein HC;Schubart U;Fine LJ
通讯作者：
Fine LJ
影响因子：
3
作者：
Ibarra-Lara, Luz;Hong, Enrique;Sanchez-Mendoza, Alicia
通讯作者：
Sanchez-Mendoza, Alicia
影响因子：
168.9
作者：
Keech, A. C.;Mitchell, P.;Colman, P. G.
通讯作者：
Colman, P. G.
DOI：
10.1056/nejmoa1001282
发表时间：
2010-04-29
期刊：
The New England journal of medicine
影响因子：
--
作者：
ACCORD Study Group;Ginsberg HN;Elam MB;Lovato LC;Crouse JR 3rd;Leiter LA;Linz P;Friedewald WT;Buse JB;Gerstein HC;Probstfield J;Grimm RH;Ismail-Beigi F;Bigger JT;Goff DC Jr;Cushman WC;Simons-Morton DG;Byington RP
通讯作者：
Byington RP
影响因子：
5
作者：
Kadian, Supriya;Mahadevan, Nanjaian;Balakumar, Pitchai
通讯作者：
Balakumar, Pitchai